The interaction of half-sandwich (η5-Cp*)Rh(III) cation with histidine containing peptides and their ternary species with (N,N) bidentate ligands

Our goal was to explore the possible interactions of potential metallodrug (η5-Cp*)Rh(III) complexes with histidine containing biomolecules (peptides/proteins) in order understand most important thermodynamic factors influencing biospeciation and biotransformation complexes. To this end, here we report systematic solution structural study on interaction cation peptides their constituents ((N-methyl)imidazole, GGA-OH, GGH-OH, histidine-amide, HGG-OH, GHG-NH2), based extensive 1H NMR, ESI-MS potentiometric investigations. The comparative evaluation our data indicated that is able induce deprotonation amide nitrogen well below pH 7. Consequently, at physiological are coordinated Rh(III) by tridentate manner, participation nitrogen. At 7.4 binding affinity follow GGA-OH < GGH-OH histidine-amide HGG-OH GHG-NH2, i.e. observed strength essentially depends presence position within peptide sequence. We also performed computational structures present near pH. all form ternary strongly coordinating (N,N) bidentate ligands (ethylenediamine or bipyridyl), which monodentately through imidazole N1‑nitrogens. In addition, strongest chelators GHG-NH2 displace these powerful from coordination sphere Rh(III).